Using isolated perfused cat lungs, we will determine the influence of dose, perfusate composition and various transport and metabolic inhibitors on the uptake and metabolism of prostaglandins of the E and F series, norepinephrine and serotonin. Single injection multiple indicator dilution experiments will be carried out in which the radiolabeled compound to be studied and an intravascular indicator are injected into the pulmonary artery and timed samples of venous effluent are obtained. The lung outflow concentration curves for the intravascular indicator and the radioactive label in parent compound and metabolite(s) will be constructed. The instantaneous extraction of the injected compound will be analyzied using a mathematical model which will provide quantitative evaluation of the kinetics of the transport process involved. The data analysis will allow us to determine the mechanisms whereby uptake and metabolism of the injected compounds are altered by experimental manipulation. During the course of the studies we will continue to develop the mathematical models used in the analysis as dictated by the experimental results.